Tertiary carbinamines (amines wherein one bond from nitrogen is to a tertiary carbon atom) are usually prepared by the addition of carbocations to nitriles [the Ritter reaction: Krimen and Cota, Org. React. 17, 213 (1969)]. This reaction requires strongly acidic conditions. In addition, the resulting acyl derivatives of the tertiary carbinamines are often difficult to hydrolyze, necessitating strongly basic conditions. The Ritter reaction is thus limited to substrates that can tolerate both strongly acidic and strongly basic conditions. Reaction of diarylketoximes with sodium in liquid nitrogen followed by alkylation gives tertiary carbinamines but the reaction is limited in scope [Gautier et al., Bull. Soc. Chim. France, 1968, 2916].
Addition of organometallic reagents, such as organolithium compounds or Grignard reagents, to nitriles usually gives imines [Layer, Chem. Rev. 63, 489 (1963); "Chemistry of the Carbon-Nitrogen Double Bond," S. Patai, Ed. Interscience, New York, N.Y., 1970, chapters 6-8]. Double addition of these reagents to nitriles to give tertiary carbinamines has been reported in only a few isolated and special cases. Thus some Grignard reagents add twice to nitriles in refluxing toluene, but imines are usually the major products and the reaction fails with benzonitrile and phenylacetonitrile [Alvernhe and Laurent, Tetrahedron Lett. 1973, 1037]. Allylmagnesium halides add twice to nitriles [Henze et al., J. Am. Chem. Soc., 65, 87, 1422 (1943); 73, 4915 (1951)], as do Grignard reagents to .alpha.-alkoxynitriles [Henze et al J. Am. Chem. Soc. 61, 1790 (1939); 73, 4915 (1951); Chastrette et al., Tetrahedron Lett. 1977, 23; Synthesis, 1980, 889; Amouroux and Axiotis, Synthesis 1981, 270], 2-hydroxybenzonitrile [Neuvonen and Pihlaja, J. Chem. Soc. Perkin 1 1988, 461] and cyanogen [Woodburn and Lathroum, J. Org. Chem. 19, 285 (1954)]. .alpha.,.alpha.-Dibutylbenzylamine is formed in low yield in the reaction of benzonitrile with n-butyllithium at room temperature [Pornet and Miginiac, Bull. Soc. Chim. France, 1975, 841].
Organometallic reagents such as organolithium compounds and Grignard reagents, do not normally add to unsubstituted imines (R.sub.2 C.dbd.NH). Tertiary carbinamines have been prepared by replacing the hydrogen atom in these imines with functionalities such as arylsulfenyl [Davis and Mancinelli, J. Org. Chem., 42, 398 (1977)] or acyl [Lipshutz et al., Tetrahedron Lett. 27, 4241 (1986)], but it is often difficult to remove these functionalities. The imine salts obtained on addition of Grignard reagents to .alpha.-alkoxynitriles react with alkyl or aryllithium reagents to give tertiary carbinamines [Gauthier et al. J. Organomet. Chem. 140, 245 1977)], but the reaction fails with other nitriles. The products obtained on addition of methyl or ethylmagnesium iodide to benzoylacetonitrile, C.sub.6 H.sub.5 COCH.sub.2 CMe(Et).dbd.NH, react with allylmagnesium bromide to give the corresponding tertiary carbinamines [Rehberg and Henze, J. Am. Chem. Soc., 63, 2785 (1941)].
The preparation of tertiary carbinamines by addition of organocerium reagents to nitriles or N-unsubstituted imines is new. The reaction of 4-cyanoacetophenone with the reagent prepared from anhydrous cerium chloride and n-butyllithium is reported to give, after 3 hours at -65.degree., only the adduct to the carbonyl group [2-(4-cyanophenyl)-2-hexanol] in 48% yield [Imamoto et al., J. Org. Chem., 49, 3904 (1984)]. The reagent prepared from n-butylmagnesium chloride and anhydrous cerium chloride adds to phenylacetonitrile only once to give the imine in low yield [Imamoto et al. J. Am. Chem. Soc., 111, 4392 (1989)]. Derivatives of secondary carbinamines have been prepared by addition of organocerium reagents to N-benzylaldimines [Reetz et al. Angew. Chem. Int. Ed. Engl., 30, 103 (1991)], N,N-disubstituted hydrazones [Denmark et al., J. Am. Chem. Soc., 109, 2224 (1987); Synlett 1989, 20], and oxime ethers [Fujioka et al., Chem. Pharm. Bull., 37, 602 (1989); Ukaji et al., Chemistry Lett., 1991, 173].